In this study, polymorphisms in the 11βHSD1 and NR3C1 genes were associated with impaired cognitive function, indicating that GC sensitivity and prereceptor regulation of GC action may play a role in the long-term consequences of CS.
Hypercortisolemia at the systemic (Cushing's syndrome) or local levels (due to adipose-specific overproduction via 11β-hydroxysteroid dehydrogenase 1) results in the preferential expansion of central, especially visceral fat depots.
The striking phenotypic similarities between metabolic syndrome and the Cushing syndrome of glucocorticoid excess have often been linked to 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates inert precursors like the cortisone, 11-dehydrocortisone to active glucocorticoids by oxo-reductase activity in several organs.
The aim of the present study was to explore presumed associations between the 83,557insA variant of the HSD11B1 gene and circulating hormone concentrations, bone turnover and bone mineral density (BMD) in patients with endogenous Cushing's syndrome (CS).
The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11β-HSD1 to avoid systemic hypercortisolism.